Cardiac arrest and cardiopulmonary resuscitation (CPR are followed by coma and early death in up to 50% of cases and in permanent brain damage in 20- 40% of survivors. The ongoing (1984-89) Brain Resuscitation Clinical Trial (BRCT) II (NS15295) is evaluating the brain damage ameliorating effect of calcium entry blocker administration to comatose cardiac arrest survivors. Current evidence indicates that earlier initiation of therapy is needed to successfully ameliorate post-ischemic brain damage. The proposed BRCT III (1989-94) will test the effects of cerebral preservation by mild hypothermia with head-neck cooling initiated during CPR, and immediate post-resuscitation reflow promotion by titrated highdose epinephrine administration during CPR. Data will be collected on 1600 cases of cardiac arrest treated in 12 hospitals. Goals of the study are; (1) to determine the ability of the previously mentioned experimental therapies,initiated both individually and in combination during CPR,to ameliorate post-ischemic brain damage: (2) to identify complications of the experimental therapies; (3) to conduct a feasibility trial of emergency,closed-chest cardiopulmonary bypass in cases of cardiac arrest resistant to standard CPR and advanced life support measures; and (4) to identify early post-arrest characteristics that accurately predict outcome. Most patients entered will have suffered sudden cardiac death outside the hospital,but in hospital arrests will also be included. Patients will be entered and randomized during CPR to one of four treatment groups (standard therapy only, high dose epinephrine,mild hypothermia,both in combination). Other than the experimental therapies,all groups will receive the same standard life support during cardiac arrest and post-resuscitation intensive care. Using methods of data collection,management and analysis adapted from BRCT II,we will compare mortality,morbidity,neurologic disability and quality of life over a six-month follow-up period between control and treatment groups. Principal outcome measures will be cerebral and overall performance categories (CPC or OPC 1 = normal; 2 = moderate disability; 3 = severe disability; 4 = vegetative state; 5 = brain death). Risks, benefits, balance of variables between groups, and adherance to protocol will be continually monitored.